Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In study I, 48 ACI and Fisher inbred rats were given MNNG 100 micrograms/ml, with or without 1 per cent or 3 per cent red pepper diet; in study II, 164 Sprague-Dawley rats given MNNG 100 micrograms/ml, with or without 5 per cent or 10 per cent NaCl; in study III, 181 Wistar rats given MNNG 83 micrograms/ml with or without maejoo 10 gm per cent/diet; in study IV, 78 Wistar rats given MNNG 83 micrograms/ml with or without ginseng extract 150 micrograms/ml; in study V, 120 Wistar rats given MNNG 83 micrograms/ml with or without retinyl palmitate 150,000 IU/kg. Except for study II (28 weeks), all rats were fed the diets for 37 weeks and were examined at 38 weeks or 40 weeks. In study I, tumor incidence in rats fed a red pepper diet and MNNG solution were 57 per cent (ACI rats, 1 per cent red pepper) and 63 per cent (Fisher rats, 1 per cent or 3 per cent red pepper) which were higher than control group (44 per cent, 43 per cent); in study II, gastric cancer, 61.9 per cent (10 per cent NaCl-MNNG), 27.3 per cent (control); in study III, gastric cancer, 14.8 per cent (maejoo-MNNG), 24 per cent (control); in study IV, malignant tumor of gastroduodenum, 3.4 per cent (ginseng-MNNG), 32.1 per cent (control); in study V, forestomach papilloma, 10.7 per cent (retinoid-MNNG), 29.4 per cent (control), and cancer in duodenum and small intestine, 50.0 per cent (retinoid-MNNG), 17.6 per cent (control). Thus, gastric carcinogenesis was enhanced by red pepper and a high salt diet, was inhibited by a maejoo and ginseng diet and was not effected by vitamin A.
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PMID:Co-carcinogenic effects of several Korean foods on gastric cancer induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats. 383 96

Relatively short-term treatment (8 weeks) of rats with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the drinking water (100 mg/l) was shown to adequately initiate gastric carcinogenesis when 10% NaCl was simultaneously administered in the diet. Utilizing this MNNG plus high salt diet as the initiation stage of a two-step protocol, it was also established that subsequent dietary administration of NaCl (10% of the diet) for 32 weeks tended to enhance tumor development in the glandular stomach. Similar tumor promoting activity was demonstrated for other mucosal damaging agents, such as potassium metabisulfite and formaldehyde. Biological changes of the gastric mucosa were examined after chronic administration or a single oral intubation of NaCl. Morphological lesions observed included diffuse mild erosions, atrophy of the glands, and hyperplasia of the foveolar epithelium when given 10% NaCl diet chronically. After a single oral intubation of NaCl, increased tritiated thymidine labeling index and ornithine decarboxylase (ODC) activity were observed in both pyloric and fundic mucosa. No remarkable effects of NaCl were observed on the forestomach or duodenal mucosa. These results suggest that NaCl exerts an enhancing effect at both initiation and promotion steps within the two stage model system of the gastric carcinogenesis, and that these effects of NaCl are possibly related to its mucosal damaging activity.
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PMID:Enhancing effects of dietary salt on both initiation and promotion stages of rat gastric carcinogenesis. 391 94

The reaction mechanisms of trans-9,10-dihydroxy-anti-7,8-epoxy-7,8,9,10-tetrahydro-3-methylcholanth rene (anti-3-MCDE) in aqueous phosphate buffer solutions (pH 7, 24 degrees C) containing double-stranded DNA, and the structure of the covalent adduct formed, were studied by utilizing the techniques of absorption, fluorescence and linear dichroism spectroscopy. The results were compared with those obtained with the widely studied trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BaPDE). The reaction mechanisms are similar in both cases since 3-MCDE also appears to form physical complexes which give rise to an acceleration of the rate of reaction of the diol-epoxide (by as much as a factor of 30 at pH 7, depending on the DNA and salt concentrations). While in the case of 3-MCDE the physical association constant is about four times lower, and the overall rate of reaction is at least five times smaller (depending on the DNA concentration) than in the case of BaPDE, the level of covalent binding is two times higher (18 +/- 2% of the 3-MCDE molecules appear as covalent adducts, the remainder forming hydrolysis products). In a novel extension of flow linear dichroism techniques, it is shown that the orientations of small aromatic moieties bound to DNA whose absorption spectra overlap with those of the nucleic acid residues below 300 nm can be studied; the dichroism at 265 nm resulting from the anthracene-like aromatic residue of 3-MCDE covalently bound to DNA suggests that its long axis tends, on average, to be tilted away from the average orientations of the planes of the nucleic acids. This conformation is similar to the one observed with adducts derived from the covalent binding of the highly tumorigenic (+) enantiomer of BaPDE, while the adducts derived from other biologically less active stereoisomers of BaPDE are characterized by conformations in which the aromatic moieties tend to be more parallel to the planes of the nucleic acid bases. Differences in the biological activities of the various polycyclic aromatic diol-epoxides are discussed in terms of these conformations and the abilities of these molecules to bind covalently to DNA.
Carcinogenesis 1986 Jan
PMID:Reaction mechanisms of trans-9,10-dihydroxy-anti-7,8-epoxy-7,8,9,10-tetrahydro-3-methylcho lan threne with DNA in aqueous solutions. Conformation of adducts. 394 43

Since the sodium salt of ascorbic acid (AA) promoted two-stage urinary bladder carcinogenesis in rats, whereas AA itself did not, the roles of the urinary sodium ion concentration and pH on urinary bladder carcinogenesis were investigated. Male F344 rats were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in their drinking water for 4 weeks and then treated with basal diet containing 5% AA plus 3% sodium bicarbonate (NaHCO3), 5% AA, 3% NaHCO3 or 5% sodium L-ascorbate (SA), 5% SA plus 1% ammonium chloride (NH4Cl) or 1% NH4Cl, or no added chemical for 32 weeks. NaHCO3 significantly increased the induction of neoplastic and preneoplastic lesions of the urinary bladder. Like SA, AA plus NaHCO3 induced high incidences of neoplastic and preneoplastic lesions of the urinary bladder, whereas AA alone did not. NH4Cl reduced the promoting activity of SA in urinary bladder carcinogenesis. These results suggest important roles for urinary sodium ion concentration and pH in modulating urinary bladder carcinogenesis. Moreover, AA was found to act as a copromoter under conditions of increased urinary pH and sodium ion concentration.
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PMID:Roles of urinary sodium ion concentration and pH in promotion by ascorbic acid of urinary bladder carcinogenesis in rats. 394 50

Seven groups of 4-week-old male Sprague-Dawley rats, 30 animals/group, were fed for 18 months a commercial chow diet with or without 1% admixture of lead subacetate (Pb-Acet) and 0, 0.3, 1, 3 and 6% of calcium acetate (CaAcet). Feeding a 3% CaAcet-only diet did not produce any pathomorphological effects except for a slight decrease in body weights of the rats to 93% of that seen in the control rats. Feeding the 1% PbAcet-only diet decreased the growth rate of rats to 80% that of the control animals and increased the organ/body weight ratios of the kidneys and livers to 200% and 114% of the corresponding control values. Kidney tumors developed in 45% of the rats treated with PbAcet only, with the earliest appearing at 58 weeks. No tumors of other tissues were found in those rats. Feeding the PbAcet + CaAcet diets reduced the weights of rats from 74% to 54% of that of the control rats and increased the kidney/body weight ratio to 300% that of the control animals. The incidences of renal tumors increased in those rats to an average of 71% (p less than 0.03 versus the PbAcet-only diet), with no significant effects relative to the CaAcet contents in the diets. Primary non-renal tumors were found only occasionally in rats fed the PbAcet + CaAcet diets, without significant differences among the various treatment groups. The renal lead accumulation at 18 months equalled 572 +/- 102, 295 +/- 43, 247 +/- 10, 168 +/- 9, and 162 +/- 6 micrograms/g dry weight (mean +/- S.E.M.; n = 22-24) for the 0, 0.3, 1, 3 and 6% CaAcet in the PbAcet diet, respectively. The hepatic accumulation of lead was 22.2 +/- 0.7 micrograms/g dry weight with no discernible differences among the various PbAcet + CaAcet treatment groups. The results indicate that CaAcet added to the PbAcet diet increases the toxicity of the lead salt, and tends to enhance the renal carcinogenicity of PbAcet, yet decreases the accumulation of lead in the kidneys. No significant adverse effects of the PbAcet and CaAcet treatments on the livers were found.
Carcinogenesis 1985 Feb
PMID:Effects of dietary calcium acetate on lead subacetate carcinogenicity in kidneys of male Sprague-Dawley rats. 397 92

Nonhistone chromosomal proteins (NHCP) from normal, regenerating rat liver, fetal liver, stages during acetylaminofluorene (AAF) and diethylnitrosamine (DEN) induced carcinogenesis, and resultant primary hepatocellular carcinomas (PHC) were analyzed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). These studies sought to determine if changes in proteins putatively involved in catalyzing specific gene expression (NHCP) occur during liver cancer development that might be related to the malignant phenotype. NHCP extracted in high salt-urea buffers, analyzed by 2D-PAGE and silver staining were resolved into some 530-560 polypeptides. Increases in number of NHCP amounting to 8.4, 8.6 and 8.8%, respectively, were detected in AAF induced nodules (AAF-NOD), AAF-PHCs and DEN-PHCs when compared to normal chromatins. The majority of the 51 qualitative changes detected reflected cell cycling and/or reexpression of fetal-NHCP. Within the total changes, seven new NHCP were found only in AAF- and DEN-induced PHCs. Further, four NHCP with isoelectric points and relative molecular weights (pI/MW) of 5.62/19.3, 5.96/30.7, 6.25/46.6 and 8.16/53.5 occurring in both AAF- and DEN-PHC also were found in AAF-NOD, a carcinogenesis stage considered to represent premalignant nodules. Reciprocally, three NHCP of pI/mol.wt.: 6.81/34.0, 5.82/43.7 and 8.18/67.0 present in normal liver, disappeared in all carcinogen involved tissues analyzed. These findings indicate that while AAF and DEN exposure results in a number of qualitative NHCP changes specific for the particular carcinogen, a total of only ten changes, seven inductions and three losses, occurred in common during hepatocarcinogenesis induced by these diverse agents. At least four of these NHCP may prove critical inductions during malignant conversion or alternatively might serve as tumor markers since they appear first in a well characterized premalignant stage and persist in resultant tumors.
Carcinogenesis 1985 Mar
PMID:Alterations in nonhistone chromatin proteins during hepatocarcinogenesis induced by diverse acting carcinogens. 397 52

A progressive accumulation of DNA breaks has been reported to occur in nuclear DNA obtained from putative premalignant hepatic lesions induced by carcinogens. To determine if this alteration resulted from a defect in the level of, or functional activity of DNA ligases, we compared these enzymes in normal rat liver, 24-h regenerating liver, and hepatic nodules at intervals after cessation of N-2-acetylaminofluorene (AAF) treatment. Nuclear extracts of hepatocytes were separated into soluble and chromatin fractions, and multiple forms of DNA ligase activity were obtained by AcA34 gel filtration chromatography. In activities of the two largest species, DNA ligase Ia (480 kd) and DNA ligase Ib (240 kd), were present exclusively in soluble, nuclear fractions and were increased 4-fold and 2-fold, respectively, in 24-h regenerating livers. In AAF-induced nodules, these species were increased 3-fold and 1.5-fold, respectively, above those of normal rat liver, somewhat higher than predicted from the rate of cell division. In all of the test tissues, these ligase species demonstrated identical sensitivity to inhibition with 0.1 M NaCl or heating at 50 degrees C. DNA ligase II (80 kd) was found in both soluble nuclear fractions and chromatin at approximately identical levels in all tissues tested. Ligase II from all tissues also demonstrated identical responses to salt and heat. These data support the concept that DNA ligases Ia and Ib are related to DNA replication and suggest that ligase II may be a repair enzyme. The failure to detect significant alterations from expected values in the hepatic nodules and the lack of alteration in sensitivity to salt and heat indicate that the accumulation of DNA damage (presumably breaks) previously observed in carcinogen-induced altered hepatocytes is not due to an alteration in the level or the biochemical properties of DNA ligase.
Carcinogenesis 1985 Sep
PMID:DNA ligase activities during hepatocarcinogenesis induced by N-2-acetylaminofluorene. 402 24

The effect of calcium(II)acetate (CaAcet) and magnesium(II) acetate (MgAcet) on nickel(II) uptake in the lungs of strain A mice and on the nickel(II)-induced changes in the pulmonary DNA synthesis were studied in order to elucidate the mechanism(s) of inhibitory action of CaAcet and MgAcet upon nickel(II) tumorigenesis. Male strain A mice received a total of three i.p. injections, one every second day, of nickel(II)acetate (NiAcet), CaAcet, or MgAcet alone, or combined in a common solution. The single doses were 43 mumol NiAcet and 430 mumol CaAcet or MgAcet/kg body weight. To determine the uptake of nickel(II) by the lungs and pulmonary subcellular fractions, NiAcet labelled with 63Ni was used and the mice were sacrificed 2 days after the last injection. The [14C]thymidine uptake by the pulmonary DNA was determined at 6 h and 1-12 days after the last injection of metal salt(s). CaAcet increased nickel(II) uptake by the pulmonary cell mitochondria by 30%, microsomes by 40% and cytosol by 15%, compared with mice given NiAcet alone; nuclear nickel(II) levels were not affected. MgAcet decreased nickel(II) uptake in the nuclei by 15% and cytosol by 25%, and had no effect on the uptake by mitochondria and microsomes. A significant decrease of thymidine incorporation into pulmonary DNA was produced by NiAcet alone and CaAcet alone at 6 h to 2 days after the injection, followed by a single round of increased thymidine incorporation between days 3 and 6 after the injection. The mixture of NiAcet and CaAcet significantly increased the thymidine incorporation into pulmonary DNA without its prodromal decrease. MgAcet alone had no influence on the uptake of thymidine into DNA, except for a slight increase on day 5; but administered together with NiAcet it completely prevented the effects of nickel(II) upon thymidine incorporation. The results provide evidence that MgAcet, but not CaAcet, may inhibit tumorigenicity of NiAcet in the lungs of strain A mice by suppressing uptake of nickel(II) by the pulmonary cell nuclei and soluble fractions, and by preventing the effects of NiAcet on pulmonary DNA synthesis.
Carcinogenesis 1985 Dec
PMID:Effects of calcium(II) and magnesium(II) on nickel(II) uptake and stimulation of thymidine incorporation into DNA in the lungs of strain A mice. 406 55

This is a review of known periods in utero during which drugs alter the process of growth; effects may be shown on the fetus or the newborn and vary with the stage of development of the fetus when exposed. Other variables are the mother and the placenta. There is no safe animal screening mechanism, the human test is by ordeal, and more clinical monitoring and reporting are needed. Cancer chemotherapeutic agents exert their maximal effects on rapidly dividing cells and are therefore hazardous during pregnancy; the greatest risk is in the 1st trimester. In the thalidomide experience the critical days were the 22nd and 23rd days after conception. Masculinizing drugs such as testosterone and other androgenic steroids have been implicated as affecting the female fetus when given early in pregnancy. Oral contraceptives taken by an already pregnant woman are a hazard because of these progestational agents. Progesterone alone is unlikely to cause masculinization but other progestins may cause such changes. Carcinogenesis may develop later in females born of mothers who are treated with diethylstilbestrol to prevent miscarriage. Many antithyroid drugs have caused neonatal goiter. Maternal ingestion of iodides during pregnancy (preparations for treating asthma, cough syrups, radio-contrast media used in diagnoses) is the most frequent cause. Goiter is relatively common in infants whose mothers were treated with propylthiouracil and other antithyroid drugs, yet they usually show normal thyroid function. However, hypothyroidism with cretinism can occur. Lithium, used in psychiatry and as a salt substitute, may alter iodine metabolism and thyroid gland function. It also passes into the milk to continue the potential toxicity. Teratogenic effects in experimental animals suggest other possible effects on infants from lithium and similar drugs.
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PMID:Human experiences related to adverse drug reactions to the fetus or neonate from some maternally administered drugs. 414 Jun 79

Malondialdehyde (MDA), a product of lipid peroxidation and prostaglandin biosynthesis, has been reported to be mutagenic and carcinogenic. Recent evidence suggests, however, that strongly mutagenic impurities are generated during the preparation of MDA that may contribute to the observed biological activity. Since MDA is widely produced in animal tissue it is important to establish whether it is actually mutagenic and carcinogenic. We have utilized three complementary methods for the preparation of highly purified MDA for biological testing. These are chromatographic purification of the sodium salt of MDA, sublimation of the free acid of MDA, and basic hydrolysis of beta-(p-nitrophenoxy)acrolein. The latter is a unique method that we have developed specifically to generate MDA under non-acidic conditions where it is stable. MDA prepared by each method induced approximately 5 revertants/mumol in Salmonella typhimurium his D 3052. This unequivocally demonstrates that MDA is a weak mutagen.
Carcinogenesis 1983
PMID:Unequivocal demonstration that malondialdehyde is a mutagen. 633 98


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